DURVALUMAB IN STAGE III NSCLC · 2020-01-04 · LUNG CANCER • Approximately 234,000 patients...
Transcript of DURVALUMAB IN STAGE III NSCLC · 2020-01-04 · LUNG CANCER • Approximately 234,000 patients...
DURVALUMAB IN STAGE III NSCLC
CASE PRESENTATION
• A 65 year old male presented with abdominal pain in March 2015
• PMH: Hypertension
• Social History: 1 pack daily since the age of 18. Alcohol use.
• CT scan of the abdomen showed a suspicious mass in the right middle lung
• CT of the chest on 6/1/15 showed a partially cavitary mass in the right mid lung and hilar and mediastinal adenopathy
• Bronchoscopy on 6/30/15‐FNA of 4R and 11R showed squamous cell carcinoma
IMAGING on 7/15/15
• Stage IIIC (T2aN3M0) squamous cell carcinoma of the right lung
• Started on concurrent radiation and Cisplatin and Etoposide
• Completed on 9/21/15
CT Chest on 9/30/15
• Patient enrolled in the PACIFIC study on 11/2/15 ‐> IV Durvalumab 10 mg/kg vs Placebo every 2 weeks for one year
• Treatment completed on 10/17/16
CT Chest on 2/24/16
CT Chest on 1/28/19
• Levothyroxine 137 mcg once daily. Most recent thyroid labs normal
• Type 2 diabetes mellitus in early 2018. On metformin and glipizide.
TSH Free T4
11/16/15 0.071 3.18
12/14/15 0.029 2.7
1/4/16 0.5 0.51
1/11/16 20.447 0.3
2/8/16 99 <0.25
2/22/16 36.396 0.56
3/7/16 2.511 1.05
Levothyroxine started
LUNG CANCER
• Approximately 234,000 patients annually• Frequency decreasing • Leading cause of cancer‐related mortality in the United States and worldwide• Over 154,000 deaths annually • Deaths declining in both men and women
Siegel RL, et.al. CA Cancer J Clin.2018.
TYPES OF LUNG CANCER
STAGE III LUNG CANCER
• 1/3 of patients
• T4 ‐ T3 N1 ‐ N2 – N3
• Unresectable (superior sulcus (Pancoast) tumor, most T4 lesions, N2 disease, N3 disease)
• Concurrent chemoradiation
• Cisplatin and Etoposide
• Weekly Carboplatin Taxol
• Cisplatin and Alimta (Nonsquamous cell lung cancer)
Belani CP, et.al. J Clin Oncol. 2005.
• Median PFS after chemoradiation 8 months
• 15% survival at 5 years
Auperin A, et.al. J Clin Oncol. 2010.
NSCLC 5‐year OS
PROGRAMMED CELL DEATH‐1 (PD‐1) and PDL‐1
CHECKPOINT INHIBITORS
• PD‐1 inhibitors‐Pembrolizumab (Keytruda)‐Nivolumab (Opdivo)‐Cemiplimab (Libtayo)
• PDL‐1 inhibitors‐Atezolizumab (Tecentriq)‐Durvalumab (Imfinzi)‐Avelumab (Bavencio)
PACIFIC TRIAL
Durvalumab after Chemoradiotherapy in Stage III Non–Small‐Cell Lung Cancer
Scott J. Antonia, et.al. N Engl J Med 2017; 377:1919‐1929
• Durvalumab had encouraging antitumor activity in early‐phase clinical study involving multiple advanced solid tumors, including stage IIIB or IV NSCLC
• Approved for patients with locally advanced or metastatic urothelial carcinoma who had received platinum‐based chemotherapy
• Preclinical evidence suggesting that chemotherapy and radiotherapy may up‐regulate PD‐L1 expression in tumor cells
Zhang P, et.al. Mol Immunol. 2008.
Progression Free survival
• 16.8 months vs 5.6 months
• 12‐month PFS rate 55.9% vs 35.3%
• 18‐month PFS rate 44.2% vs 27.0%
• ORR 28.4% vs. 16.0%
• Longer duration of response.
• 24‐month overall survival rate 66.3% vs 55.6%
POSSIBLE SIDE EFFECTS
Adverse events: 96.8% vs 94.9%
Grade 3 or 4 adverse events: 29.9% vs 26.1%
Pneumonia: 4.4% vs 3.8%
IMMUNOTHERAPY IN NSCLC• Stage IV disease. First line treatment.
• Pembrolizumab vs Platinum based therapy (Keynote‐024)‐PDL‐1: 50% or more‐Follow up 11.2 months, PFS 10.3 vs 6 months ‐Further follow up, OS 30 vs 14.2 months
• Carboplatin, Pemetrexed with Pembrolizumab or Placebo (Keynote‐189)‐PFS 8.8 vs 4.9 months ‐12 month OS 69.2% vs 49%.
• Carboplatin, Taxol, and Avastin with Atezolizumab or Placebo (IMpower150)‐PFS 8.3 vs 6.8 months‐OS 19.2 versus 14.7 months
Reck M, et.al. N Engl J Med. 2016.
Socinski MA, et.al. N Engl J Med. 2018.
IMMUNOTHERAPY IN NSCLC
• Carboplatin, Taxol/Abraxane with either Pembrolizumab or placebo (Keynote‐407) ‐OS 15.9 vs 11.3 months‐PSF 6.4 vs 4.8 months
Paz‐AresL, et.al. N Engl J Med.2018.
IMMUNOTHERAPY IN NSCLC• Recurrent disease
• Nivolumab versus Docetaxel (Checkmate trial)
• Nonsquamous histology‐OS 12.2 versus 9.4 months‐ORR 19 versus 12%‐Duration of response 18 versus 6 months
• Squamous histology• Nivolumab versus Docetaxel • OS 9.2 vs 6.0 months• ORR 20 vs 9%• Duration of response 25 versus 8 months
Brahmer J, et.al. N Engl J Med. 2015.
Horn, et.al. J Clin Oncol.2015.
IMMUNOTHERAPY IN NSCLC
• Pembrolizumab vs Docetaxel (Keynote‐010)‐OS 10.4 and 12.7 months for Pembrolizumab low and high dose vs 8.5 months‐Median PFS similar (4 months)‐Better tolerated
• Atezolizumab versus Docetaxel‐OS 13.8 versus 9.6 months‐Duration of response 16.3 vs 6.2 months‐PFS 2.8 vs 4 months‐ORR 14 vs 13 percent
Herbst RS, Baas P, et.al. Lancet. 2016.
Rittmeyer A, et.al. Lancet. 2017.
• Durvalumab is standard maintenance treatment in stage III NSCLC
• Immunotherapy plays major role in stage IV NSCLC in the first line setting and also in recurrence
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